A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected thais
Background: CD8+ T cell responses play an important role in the control of HIV-1. The extensive sequence diversity of HIV-1 represents a critical hurdle to developing an effective HIV-1 vaccine, and it is likely that regional-specific vaccine strains will be required to overcome the diversity of the...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1826259966146641920 |
|---|---|
| author | Buranapraditkun, S Hempel, U Pitakpolrat, P Allgaier, R Thantivorasit, P Lorenzen, S Sirivichayakul, S Hildebrand, W Altfeld, M Brander, C Walker, B Phanuphak, P Hansasuta, P Rowland-Jones, S Allen, T Ruxrungtham, K |
| author_facet | Buranapraditkun, S Hempel, U Pitakpolrat, P Allgaier, R Thantivorasit, P Lorenzen, S Sirivichayakul, S Hildebrand, W Altfeld, M Brander, C Walker, B Phanuphak, P Hansasuta, P Rowland-Jones, S Allen, T Ruxrungtham, K |
| author_sort | Buranapraditkun, S |
| collection | OXFORD |
| description | Background: CD8+ T cell responses play an important role in the control of HIV-1. The extensive sequence diversity of HIV-1 represents a critical hurdle to developing an effective HIV-1 vaccine, and it is likely that regional-specific vaccine strains will be required to overcome the diversity of the different HIV-1 clades distributed world-wide. Unfortunately, little is known about the CD8+ T cell responses against CRF01_AE, which is responsible for the majority of infections in Southeast Asia. Methodology/Principal Findings: To identify dominant CD8+ T cell responses recognized in HIV-1 clade CRF01_AE infected subjects we drew upon data from an immunological screen of 100 HIV-1 clade CRF01_AE infected subjects using IFN-gamma ELISpot to characterize a novel immunodominant CD8+ T cell response in HIV-1 Gag restricted by HLA-Cw*0102 (p24, 277YSPVSILDI 285, YI9). Over 75% of Cw*0102+ve subjects targeted this epitope, representing the strongest response in more than a third of these individuals. This novel CD8 epitope was located in a highly conserved region of HIV-1 Gag known to contain immunodominant CD8 epitopes, which are restricted by HLA-B*57 and -B*27 in clade B infection. Nonetheless, viral escape in this epitope was frequently observed in Cw*0102+ve subjects, suggestive of strong selection pressure being exerted by this common CD8+ T cell response. Conclusions/Significance: As HLA-Cw*0102 is frequently expressed in the Thai population (allelic frequency of 16.8%), this immunodominant Cw*0102-restricted Gag epitope may represent an attractive candidate for vaccines specific to CRF01_AE and may help facilitate further studies of immunopathogenesis in this understudied HIV-1 clade. © 2011 Buranapraditkun et al. |
| first_indexed | 2024-03-06T18:58:10Z |
| format | Journal article |
| id | oxford-uuid:12948d02-db82-48e9-bf05-54769d867ff6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:58:10Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:12948d02-db82-48e9-bf05-54769d867ff62022-03-26T10:08:50ZA novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected thaisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:12948d02-db82-48e9-bf05-54769d867ff6EnglishSymplectic Elements at Oxford2011Buranapraditkun, SHempel, UPitakpolrat, PAllgaier, RThantivorasit, PLorenzen, SSirivichayakul, SHildebrand, WAltfeld, MBrander, CWalker, BPhanuphak, PHansasuta, PRowland-Jones, SAllen, TRuxrungtham, KBackground: CD8+ T cell responses play an important role in the control of HIV-1. The extensive sequence diversity of HIV-1 represents a critical hurdle to developing an effective HIV-1 vaccine, and it is likely that regional-specific vaccine strains will be required to overcome the diversity of the different HIV-1 clades distributed world-wide. Unfortunately, little is known about the CD8+ T cell responses against CRF01_AE, which is responsible for the majority of infections in Southeast Asia. Methodology/Principal Findings: To identify dominant CD8+ T cell responses recognized in HIV-1 clade CRF01_AE infected subjects we drew upon data from an immunological screen of 100 HIV-1 clade CRF01_AE infected subjects using IFN-gamma ELISpot to characterize a novel immunodominant CD8+ T cell response in HIV-1 Gag restricted by HLA-Cw*0102 (p24, 277YSPVSILDI 285, YI9). Over 75% of Cw*0102+ve subjects targeted this epitope, representing the strongest response in more than a third of these individuals. This novel CD8 epitope was located in a highly conserved region of HIV-1 Gag known to contain immunodominant CD8 epitopes, which are restricted by HLA-B*57 and -B*27 in clade B infection. Nonetheless, viral escape in this epitope was frequently observed in Cw*0102+ve subjects, suggestive of strong selection pressure being exerted by this common CD8+ T cell response. Conclusions/Significance: As HLA-Cw*0102 is frequently expressed in the Thai population (allelic frequency of 16.8%), this immunodominant Cw*0102-restricted Gag epitope may represent an attractive candidate for vaccines specific to CRF01_AE and may help facilitate further studies of immunopathogenesis in this understudied HIV-1 clade. © 2011 Buranapraditkun et al. |
| spellingShingle | Buranapraditkun, S Hempel, U Pitakpolrat, P Allgaier, R Thantivorasit, P Lorenzen, S Sirivichayakul, S Hildebrand, W Altfeld, M Brander, C Walker, B Phanuphak, P Hansasuta, P Rowland-Jones, S Allen, T Ruxrungtham, K A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected thais |
| title | A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected thais |
| title_full | A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected thais |
| title_fullStr | A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected thais |
| title_full_unstemmed | A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected thais |
| title_short | A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected thais |
| title_sort | novel immunodominant cd8 t cell response restricted by a common hla c allele targets a conserved region of gag hiv 1 clade crf01 ae infected thais |
| work_keys_str_mv | AT buranapraditkuns anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT hempelu anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT pitakpolratp anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT allgaierr anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT thantivorasitp anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT lorenzens anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT sirivichayakuls anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT hildebrandw anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT altfeldm anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT branderc anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT walkerb anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT phanuphakp anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT hansasutap anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT rowlandjoness anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT allent anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT ruxrungthamk anovelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT buranapraditkuns novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT hempelu novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT pitakpolratp novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT allgaierr novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT thantivorasitp novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT lorenzens novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT sirivichayakuls novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT hildebrandw novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT altfeldm novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT branderc novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT walkerb novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT phanuphakp novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT hansasutap novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT rowlandjoness novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT allent novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais AT ruxrungthamk novelimmunodominantcd8tcellresponserestrictedbyacommonhlacalleletargetsaconservedregionofgaghiv1cladecrf01aeinfectedthais |